Conformational heterogeneity of the p53 tumor suppressor, wild-type and mutated forms, was investigated by computational modelling combined with all atoms Molecular Dynamics (MD) simulations. Four different punctual mutations (p53R175H, p53R248Q, p53R273H, p53R282W), which are known to affect the DNA binding and belong to the most frequent hot-spot mutations in human cancers, were taken into consideration. The MD trajectories of the wild-type and mutated p53 forms were analysed by Essential Dynamics, to extract relevant collective motions. The same trajectories were also analysed by the frustration method which allows to evaluate the degeneracy of the energy landscape. We found that punctual mutations can modulate the collective motions of p53 at different extent according to the specific mutation. Furthermore, mutations can affect the frustration level of p53 specially in the regions involved in the binding to physiological ligands. The regions of p53 with larger collective motions are also characterized by a high frustration level. The regions of p53 characterized by a high frustration level are also largely involved in wide collective motions. Such a correlation is discussed in connection with the intrinsic disordered character of p53 and also with its central functional role.